Throughout this application various publications are referred to in parentheses. Full citations for these references may be found at the end of the specification. The disclosures of these publications, and all patents, patent application publications and books referred to herein, are hereby incorporated by reference in their entirety into the subject application to more fully describe the art to which the subject invention pertains.
Cell surface receptors and adhesion molecules are the gatekeepers of cellular function, including developmental, morphogenetic and environmental processes central to normal physiology and pathology. These molecules are prime therapeutic targets. The high-resolution structural characterization of these complexes defines the chemical and physical determinants underlying receptor:ligand specificity, affinity, oligomeric state, valency and overall architectural features that are important for the integration of these interactions and their associated signaling pathways into overall cellular physiology. All of these features are critical for understanding the fundamental mechanisms that drive complex cellular processes and provide unique opportunities for therapeutic intervention. Unfortunately, at present, a systematic structural characterization of these crucial complexes (i.e., structural genomics of the Secretome) is an unrealistic goal, as many, if not most, receptor:ligand pairs remain undefined and thus cannot be structurally characterized.
The present invention addresses this need by providing technologies for the efficient and systematic identification of the repertoire of receptor:ligand interactions relevant to human physiology, disease and medicine.